Self-Assembly of Chiral Porous Metal-Organic Polyhedra from Trianglsalen Macrocycles.

Metal-organic polyhedra (MOPs) can exhibit tunable porosity and functionality, suggesting potential for applications such as molecular separations. MOPs are typically constructed by the bottom-up multicomponent self-assembly of organic ligands and metal ions, and the final functionality can be hard to program. Here, we used trianglsalen macrocycles as preorganized building blocks to assemble octahedral-shaped MOPs. The resultant MOPs inherit most of the preorganized properties of the macrocyclic ligands, including their well-defined cavities and chirality. As a result, the porosity in the MOPs could be tuned by modifying the structure of the macrocycle building blocks. Using this strategy, we could systematically enlarge the size of the MOPs from 26.3 to 32.1 Å by increasing the macrocycle size. The family of MOPs shows experimental surface areas of up to 820 m2/g, and they are stable in water. One of these MOPs can efficiently separate the rare gases Xe from Kr because the prefabricated macrocyclic windows of MOPs can be modified to sit at the Xe/Kr size cutoff range.

Recent developments in ureteral stent: Substrate material, coating polymer and technology, therapeutic function.

The ureteral stent is an effective treatment for clinical ureteral stricture following urological surgery, and the functional coating of the stent could effectively inhibit bacterial colonization and other complications. The present review provides an analysis and description of the materials used in ureteral stents and their coatings. Emphasis is placed on the technological advancements of functional coatings, taking into consideration the characteristics of these materials and the properties of their active substances. Furthermore, recent advances in enhancing the therapeutic efficacy of functional coatings are also reviewed. It is anticipated that this article will serve as a valuable reference providing insights for future research development on new drug-loaded ureteral stents.

The Science of Precision Prevention: Research Opportunities and Clinical Applications to Reduce Cardiovascular Health Disparities.

Precision prevention embraces personalized prevention but includes broader factors such as social determinants of health to improve cardiovascular health. The quality, quantity, precision, and diversity of data relatable to individuals and communities continue to expand. New analytical methods can be applied to these data to create tools to attribute risk, which may allow a better understanding of cardiovascular health disparities. Interventions using these analytic tools should be evaluated to establish feasibility and efficacy for addressing cardiovascular disease disparities in diverse individuals and communities. Training in these approaches is important to create the next generation of scientists and practitioners in precision prevention. This state-of-the-art review is based on a workshop convened to identify current gaps in knowledge and methods used in precision prevention intervention research, discuss opportunities to expand trials of implementation science to close the health equity gaps, and expand the education and training of a diverse precision prevention workforce.

Unilateral contrast-induced encephalopathy with contrast medium exudation: A case report.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare transient, reversible abnormality in the structure or function of the nervous system caused by the intravascular use of contrast agents. CIE can present with a range of neurological manifestations, including focal neurological deficits (hemiplegia, hemianopia, cortical blindness, aphasia, and parkinsonism) and systemic symptoms (confusion, seizures, and coma). However, if not accurately diagnosed and treated in a timely manner, CIE can cause irreversible damage to patients, especially critically ill patients. CASE SUMMARY: A male in his 50 s, 2 h after digital subtraction angiography, had a progressive disorder of consciousness, mixed aphasia, bilateral pupillary sluggish light reflex, and right limb weakness. Seven hours after the procedure, he developed unconsciousness, high fever (39.5 °C), seizures, hemiplegia, neck stiffness (+), and right Babinski signs (+). computed tomography (CT) findings 2 h postprocedure were very confusing and led us to misdiagnose the patient with subarachnoid hemorrhage. Brain CT was performed again 7 h after the procedure. Compared with the CT 2 h after the procedure, the CT 7 h after the procedure showed that the manifestations of subarachnoid hemorrhage in the left cerebral hemisphere had disappeared and were replaced by brain tissue swelling, and the cerebral sulci had disappeared. Combined with the clinical manifestations of the patient and after the exclusion of subarachnoid hemorrhage and cerebrovascular embolism, we diagnosed the patient with CIE, and intravenous fluids were given for adequate hydration, as well as mannitol, albumin dehydration, furosemide and the glucocorticoid methylprednisolone. After 17 d of active treatment, the patient was discharged with no sequelae. CONCLUSION: CIE should be taken seriously, but it is easily misdiagnosed, and once CIE is diagnosed, rapid, accurate diagnosis and treatment are critical steps. Whether a follow-up examination using a contrast agent can be performed should be closely evaluated, and the patient should be fully informed of the associated risks.

KEBLM: Knowledge-Enhanced Biomedical Language Models.

Pretrained language models (PLMs) have demonstrated strong performance on many natural language processing (NLP) tasks. Despite their great success, these PLMs are typically pretrained only on unstructured free texts without leveraging existing structured knowledge bases that are readily available for many domains, especially scientific domains. As a result, these PLMs may not achieve satisfactory performance on knowledge-intensive tasks such as biomedical NLP. Comprehending a complex biomedical document without domain-specific knowledge is challenging, even for humans. Inspired by this observation, we propose a general framework for incorporating various types of domain knowledge from multiple sources into biomedical PLMs. We encode domain knowledge using lightweight adapter modules, bottleneck feed-forward networks that are inserted into different locations of a backbone PLM. For each knowledge source of interest, we pretrain an adapter module to capture the knowledge in a self-supervised way. We design a wide range of self-supervised objectives to accommodate diverse types of knowledge, ranging from entity relations to description sentences. Once a set of pretrained adapters is available, we employ fusion layers to combine the knowledge encoded within these adapters for downstream tasks. Each fusion layer is a parameterized mixer of the available trained adapters that can identify and activate the most useful adapters for a given input. Our method diverges from prior work by including a knowledge consolidation phase, during which we teach the fusion layers to effectively combine knowledge from both the original PLM and newly-acquired external knowledge using a large collection of unannotated texts. After the consolidation phase, the complete knowledge-enhanced model can be fine-tuned for any downstream task of interest to achieve optimal performance. Extensive experiments on many biomedical NLP datasets show that our proposed framework consistently improves the performance of the underlying PLMs on various downstream tasks such as natural language inference, question answering, and entity linking. These results demonstrate the benefits of using multiple sources of external knowledge to enhance PLMs and the effectiveness of the framework for incorporating knowledge into PLMs. While primarily focused on the biomedical domain in this work, our framework is highly adaptable and can be easily applied to other domains, such as the bioenergy sector.

A hypochlorite-activated strategy for realizing fluorescence turn-on, type I and type II ROS-combined photodynamic tumor ablation.

The combination of cancer cell-activated fluorescence and the advantages of both type I and type II photodynamic therapy (PDT) capabilities to achieve a synergistic therapeutic effect in a complex tumor environment is highly desirable. Herein, we report an approach by means of tumor intracellular hypochlorite (ClO-) to turn on fluorescence integrated with type I and II ROS generation for imaging-guided PDT. The resultant PTZSPy functions as a type II photosensitizer with mitochondria-targeting capability. In the presence of ClO-, PTZSPy is transformed into its oxidized counterpart SPTZSPy, turns on an orange-red fluorescence and triggers the type I ROS generation ability. Biological studies revealed that PTZSPy can accurately distinguishes tumor cells from normal cells, dynamically monitors the cell ablation process and be utilized for theranostics in MCF-7 tumor-bearing nude mice in vivo. This work provides an innovative strategy exploiting the highly abundant ClO- in tumor cells for the type I and II ROS two-pronged and imaging-guided PDT.

Follicular lymphoma with cardiac involvement in a 90-year-old patient: A case report.

BACKGROUND: The incidence of cardiac lymphoma is low, and it mainly occurs secondary to non-Hodgkin's lymphoma, particularly diffuse large B-cell lymphoma. Here, we report a case of follicular lymphoma with cardiac involvement and severe heart failure as the sole clinical manifestation. CASE SUMMARY: A 90-year-old male patient was first admitted to our hospital due to an accidentally discovered painless mass in the right lower abdomen. A biopsy of the mass revealed a follicular lymphoma. Positron emission tomography-computed tomography confirmed mild pericardial effusion, and echocardiography showed no structural abnormalities with normal ejection fraction at the time of diagnosis. The patient refused our recommendation of chemotherapy and was re-admitted 4 mo later due to heart failure. A series of subsequent echocardiographic examinations showed thickening of the left ventricular walls and increasing pericardial effusion over the following 2 mo. His heart failure exacerbated despite all symptomatic and supportive treatments. He passed away after an episode of aspiration pneumonia. CONCLUSION: The diagnosis of cardiac lymphoma is difficult as its clinical manifestations are nonspecific, and prognosis is poor.

Dynorphin promotes stress-induced depressive behaviors by inhibiting ventral pallidal neurons in rats.

AIM: Endogenous dynorphin signaling via kappa opioid receptors (KORs) plays a key role in producing the depressive and aversive consequences of stress. We investigated the behavioral effects of the dynorphin/KOR system in the ventral pallidum (VP) and studied the underlying mechanisms. METHODS: To investigate the effects of dynorphin on the VP, we conducted behavioral experiments after microinjection of drugs or shRNA and brain-slice electrophysiological recordings. Histological tracing and molecular biological experiments were used to identify the distribution of KORs and the possible sources of dynorphin projections to the VP. RESULTS: An elevated dynorphin concentration and increased KOR activity were observed in the VP after acute stress. Infusion of dynorphin-A into the VP produced depressive-like phenotypes including anhedonia and despair and anxiety behaviors, but did not alter locomotor behavior. Mechanistically, dynorphin had an inhibitory effect on VP neurons-reducing their firing rate and inhibiting excitatory transmission-through direct activation of KORs and modulation of downstream G-protein-gated inwardly rectifying potassium (GIRK) channels and high-voltage gated calcium channels (VGCCs). Tracing revealed direct innervation of VP neurons by dynorphin-positive projections; potential sources of these dynorphinergic projections include the nucleus accumbens, amygdala, and hypothalamus. Blockade of dynorphin/KOR signaling in the VP by drugs or viral knock-down of KORs significantly reduced despair behavior in rats. CONCLUSIONS: Endogenous dynorphinergic modulation of the VP plays a critical role in mediating depressive reactions to stress.

Hope During the COVID-19 Epidemic Decreased Anxiety and Depression Symptoms Mediated by Perceived Stress: Coping Style Differences Among Patients with COVID-19.

OBJECTIVE: This study aimed to investigate whether perceived stress mediated the relationship between hope and anxiety/depression symptoms among patients with COVID-19 during the epidemic. In addition, the potential moderating effect of coping styles was examined. METHODS: From February 26 to March 10, 2020, patients with COVID-19 were asked to complete a questionnaire online, which included demographic characteristics, as well as the SCL-90-Anxiety, SCL-90-Depression, Chinese Perceived Stress Scale (CPSS), Herth Hope Index (HHI), and Trait Coping Style Questionnaire (TCSQ). Hierarchical linear regression was performed to explore independent factors of anxiety/depression. A multi-group structural equation modeling with the collected data from patients in the Negative Coping style (NC) group and Positive Coping style (PC) group was used to test the hypothesized mechanism. RESULTS: In total, 382 valid questionnaires of patients were obtained, including 96 from NC patients and 286 from PC patients. In the hierarchical linear regression, hope and perceived stress were independent risk factors for both anxiety and depression in the total sample and PC group. However, hope was not independently related to anxiety/depression in the NC group. As hypothesized, the hope of patients had significant and negative indirect effects on both anxiety and depression that were mediated by perceived stress, However, the direct effect from stress on anxiety and depression was stronger for NC patients than for PC patients. Besides, hope had significant direct effects on anxiety/depression in PC patients, but not in NC patients. CONCLUSION: During the COVID-19 epidemic, perceived stress could mediate the relationship between hope and anxiety/depression symptoms among COVID-19 patients, with coping style moderating this cultivation process.

[Effects of Nitrogen Fertilizer Application Times and Nitrification Inhibitor on N2O Emission from Potted Maize].

Rational application of nitrogen is an important strategy for increasing yield while reducing environmental pollution due to nitrogen. Pot experiments were conducted to study the effects of different application times on maize yield and soil N2O emission under conditions of equal nitrogen content, and to explore the relationship between the abundance of nitrogen conversion functional genes and N2O emission. Four treatments were used, namely a control (CK, no urea), one-time application (S1, one application of 0.5 g·kg-1 urea+nitrification inhibitor), two separate applications ï¼»S2, two applications of 0.5 g·kg-1 urea (40% and 60% respectively)ï¼½ and three separate applications (S3, 0.5 g·kg-1 urea was divided into three different applications: 20%, 40% and 40% respectively). The results showed that: ① nitrogen application promoted soil acidification, and the degree of soil acidification varied significantly with different application times. More applications of nitrogen led to stronger soil acidification. Nitrogen application significantly increased the ear yield and stem biomass of fresh table maize, but different nitrogen application times may alter soil pH, leading to differences in the degree of nitrogen uptake and utilization in plants. While the S3 treatment significantly reduced soil pH, it also reduced the cumulative nitrogen uptake and utilization in the plants, resulting in a high cumulative N2O emission. Compared with the S3 treatment, the yield was 40.21% and 42.55% higher in the S1 and S2 treatments, and the cumulative N2O emission decreased by 79.4% and 20.9%, respectively. ② N2O emission was positively correlated with the abundance of AOB and nirK genes, which were the main contributors to N2O emission. S1 significantly decreased the abundance of AOB and nirK genes and N2O emissions, while S2 and S3 significantly increased the abundance of nirK and nirS genes and decreased the abundance of nosZ genes after fertilization, promoting N2O emissions. Nitrogen application times affect the functional genes of the nitrogen transformation process, and thus affect N2O emissions. In conclusion, a one-time application of urea combined with DCD only guarantees high maize yield and improves the efficient use of nitrogen, but also reduces greenhouse gas emissions. Thus, it is the recommended nitrogen fertilization mode for the cultivation of fresh corn in Hainan.

Identification of Antitumor Constituents in Toad Venom by Spectrum-Effect Relationship Analysis and Investigation on Its Pharmacologic Mechanism.

(1) Background: Toad venom (Bufonis Venenum, known as 'Chansu' in Chinese), the secretion of the ear-side gland and skin gland of Bufo gargarizans cantor or Duttaphrynus melanostictus Schneider, has been utilized to treat several diseases in China for thousands of years. However, due to the chemical variability of the components, systematic chemical composition and the key pharmacophores in toad venom have not yet fully understood. Besides, it contains a variety of effective compounds with different physiological activity and chemotypes, mainly including alkaloids, bufogenins, bufotoxins, and so on. The recent pharmacological researches have demonstrated that several bufogenins have remarkable pharmacological effects, such as anti-inflammatory, analgesic effects, and anti-tumor effects. Aim of the study: To identify the bioactive compounds and pharmacophores originating from toad venom based on analyzing spectrum-effect relationship by chemometrics and to explore the anti-cancer mechanism primarily. (2) Materials and methods: Fingerprint of the 21 batches of samples was established using HPLC (High Performance Liquid Chromatography). The anti-tumor activity of extracts were determined by in-vitro assays. Chemometric analysis was used to establish the spectrum-effect model and screen for active ingredients. Pharmacodynamic tests for the screened active compound monomers were conducted with in-vitro assays. Further anti-tumor mechanisms were investigated using western blot and flow cytometry. (3) Results: The established spectrum-effect model has satisfactory fitting effect and predicting accuracy. The inhibitory effect of major screened compounds on lung carcinoma cells A549 were validated in vitro, demonstrating that arenobufagin, telocinobufogenin, and cinobufotalin had significant anti-tumor effects. Through further investigation of the mechanism by western blotting and flow cytometry, we elucidated that arenobufagin induces apoptosis in A549 cells with the enhanced expression of cleaved PARP (poly (ADP-ribose) polymerase). These results may provide valuable information for further structural modification of bufadienolides to treat lung cancer and a method for discovery of anti-tumor active compounds. Conclusions: Our research offers a more scientific method for screening the principal ingredients dominating the pharmacodynamic function. These screened compounds (arenobufagin, etc.) were proven to induce apoptosis by overactivation of the PARP-pathway, which may be utilized to make BRCA (breast cancer susceptibility gene) mutant cancer cells more vulnerable to DNA damaging agents and kill them.

Correlation between age of onset and gastrointestinal stenosis in hospitalized patients with Crohn's disease.

BACKGROUND: Patients affected by Crohn's disease (CD) are more likely to develop gastrointestinal stenosis and often undergo surgery during the duration of disease. AIM: To identify the risk factors for gastrointestinal stenosis in hospitalized CD patients in China. METHODS: The clinical data of CD patients hospitalized at the Seventh Medical Center, Chinese People's Liberation Army General Hospital from January 2010 to December 2018 were included. Patients with gastrointestinal stenosis were compared to those without gastrointestinal stenosis for clinical variables. The risk factors for gastrointestinal stenosis were identified using univariate and multivariable logistic regression analyses. The treatments for patients with gastrointestinal stenosis were analyzed, and the characteristics of different treatment methods were discussed. RESULTS: The incidence of gastrointestinal stenosis was 59.02% in the 122 hospitalized CD patients. Age of onset of more than 40 years (odds ratio [OR] = 3.072, 95% confidence interval [CI]: 1.298-7.272, P = 0.009) and duration of disease of more than 5 years (OR = 2.101, 95%CI: 1.002-4.406, P = 0.048) were associated with the occurrence of gastrointestinal stenosis. Fifteen (20.83%) patients did not undergo surgery and received internal medicine and nutrition treatment. Surgical treatments were performed in 72.22% (52) of cases. The rate of postoperative complications was 15.38% (8 cases), and during a median follow-up period of 46 mo, 11.54% (6 cases) underwent reoperation. A total of 29.17% (21 cases) were treated with endoscopic therapy, and during a median follow-up period of 32 mo, 76.19% (16 cases) had no surgical event, 23.81% (5 cases) failed to avoid surgical treatments, and no serious postoperative complications occurred after endoscopic therapy. CONCLUSION: Age of onset of more than 40 years and duration of disease of more than 5 years may be strongly correlated with a higher risk of gastrointestinal stenosis in hospitalized CD patients. Endoscopic therapy for gastrointestinal stenosis is relatively safe and effective, and may help to prevent or delay surgery.

18F-fluorodeoxyglucose positron emission tomography/computed tomography-based radiomic features for prediction of epidermal growth factor receptor mutation status and prognosis in patients with lung adenocarcinoma.

BACKGROUND: To investigate whether radiomic features from (18F)-fluorodeoxyglucose positron emission tomography/computed tomography [(18F)-FDG PET/CT] can predict epidermal growth factor receptor (EGFR) mutation status and prognosis in patients with lung adenocarcinoma. METHODS: One hundred and seventy-four consecutive patients with lung adenocarcinoma underwent (18F)-FDG PET/CT and EGFR gene testing were retrospectively analyzed. Radiomic features combined with clinicopathological factors to construct a random forest (RF) model to identify EGFR mutation status. The mutant/wild-type model was trained on a training group (n=139) and validated in an independent validation group (n=35). The second RF classifier predicting the 19/21 mutation site was also built and evaluated in an EGFR mutation subset (training group, n=80; validation group, n=25). Radiomic score and 5 clinicopathological factors were integrated into a multivariate Cox proportional hazard (CPH) model for predicting overall survival (OS). AUC (the area under the receiver characteristic curve) and C-index were calculated to evaluate the model's performance. RESULTS: Of 174 patients, 109 (62.6%) harbored EGFR mutations, 21L858R was the most common mutation type [55.9% (61/109)]. The mutant/wild-type model was identified in the training (AUC, 0.77) and validation (AUC, 0.71) groups. The 19/21 mutation site model had an AUC of 0.82 and 0.73 in the training and validation groups, respectively. The C-index of the CPH model was 0.757. The survival time between targeted therapy and chemotherapy for patients with EGFR mutations was significantly different (P=0.03). CONCLUSIONS: Radiomic features based on (18F)-FDG PET/CT combined with clinicopathological factors could reflect genetic differences and predict EGFR mutation type and prognosis.

Long-term low-dose ethanol intake improves healthspan and resists high-fat diet-induced obesity in mice.

Numerous epidemiological studies have reported that moderate alcohol drinking has beneficial effects. However, few studies have focused on the beneficial effects of ethanol, the common component in alcoholic beverages. Here we fed the C57BL/6 mice with 3.5% v/v ethanol as drinking water substitute to investigate the effects of long-term low-dose ethanol intake in vivo. We evaluated the metabolic rate and mitochondrial function of the long-term low-dose ethanol-intake (LLE) mice, assessed the exercise ability of LLE mice, and fed the LLE mice with a high-fat diet to investigate the potential impact of ethanol on it. The LLE mice showed improved thermogenic activity, physical performance, and mitochondrial function, as well as resistance against the high-fat diet-induced obesity with elevated insulin sensitivity and subdued inflammation. Our results suggest that long-term low-dose ethanol intake can improve healthspan and resist high-fat diet-induced obesity in mice. It may provide new insight into understanding the protective effects of moderate alcohol drinking.

Low-dose ethanol intake prevents high-fat diet-induced adverse cardiovascular events in mice.

A high-fat diet is recognized as an important factor in the development of cardiovascular diseases including cardiomyopathy. Besides high-fat diets, large quantities of ethanol also induce cardiomyopathy in both animals and humans. Emerging evidence suggests that low ethanol intake may have a protective effect on the cardiovascular system. This study aimed to clarify whether low-dose ethanol intake could prevent high-fat diet-induced adverse effects on cardiomyocytes in mice. After 6-8 weeks of feeding, the heart weight significantly decreased in ethanol + HFD mice compared to HFD mice. In addition, cardiac triglycerides and lipid droplets also decreased, but no statistically significant difference in cholesterol level was found between the two groups. Expression of the fatty acid transporters Cd36, Slc27a1 and Got2 was downregulated in the ethanol + HFD group. According to echocardiography, the mass and volume of the left ventricle were reduced, and the ejection fraction (EF) and fractional shortening (FS) were increased in mice fed with alcohol. Low doses of ethanol reduced the cardiomyocytes' cross-sectional area and the expression of the hypertrophic markers ANP and BNP. Moreover, Col1a1, the main collagen type expressed in the heart, was also reduced by low-dose ethanol consumption. Also, the expression of Rgs5, a crucial component of the signaling pathway involved in cardiac remodeling and heart failure, was upregulated in response to ethanol intake. The data suggest that low ethanol intake prevents adverse effects induced by a high-fat diet, such as lipid accumulation, cardiac dysfunction, hypertrophy and fibrosis. Furthermore, low ethanol intake upregulates Rgs5, which suggests it plays a role in cardiac remodeling and heart failure.

Combined surgical and interventional treatment of tandem carotid artery and middle cerebral artery embolus: A case report.

BACKGROUND: The 2018 American Heart Association/American Stroke Association guidelines for early management of acute ischemic stroke recommend the use of retrievable stents for mechanical thrombectomy in patients with acute internal carotid artery or middle cerebral artery M1 occlusion that can be treated within 6 h from onset. For cases of carotid artery with ipsilateral middle cerebral artery tandem embolization, the operation is more complicated and challenging. We here report a case of a tandem embolism, and the anatomy of the aortic arch was complex. Direct carotid artery incision and thrombectomy can not only prevent the escape of the carotid embolus but also save time during establishment of the thrombectomy access. CASE SUMMARY: The patient was a 70-year-old man. He was admitted to hospital due to sudden inability to speak and inability to move his right limb for 3 h. Imaging confirmed a diagnosis of a tandem embolism in the left carotid artery with left M1 occlusion. Carotid artery incision thrombectomy combined with stent thrombectomy was performed. The operation was successful, and 24 h later the patient was conscious and mentally competent but had motor aphasia. His bilateral limb muscle strength level was 5, and his neurologic severity scores score was 2. CONCLUSION: Carotid artery incision thrombectomy combined with stenting for carotid artery plus cerebral artery tandem embolization is clinically feasible. For patients with a complicated aortic arch and an extremely tortuous carotid artery, carotid artery incision can be chosen to establish the interventional path.

Mechanics and Biology Interact in Intervertebral Disc Degeneration: A Novel Composite Mouse Model.

The aim of this study was to distinguish the characteristics of intervertebral disc degeneration (IVDD) originating from mechanics imbalance, biology disruption, and their communion, and to develop a composite IVDD model by ovariectomy combined with lumbar facetectomy for mimicking elderly IVDD with osteoporosis and lumbar spinal instability. Mice were randomly divided into four groups and subjected to sham surgery (CON), ovariectomy (OVX), facetectomy (mechanical instability, INS) or their combination (COM), respectively. Radiographical (n = 4) and histological changes (n = 8) of L4/5 spinal segments were analyzed. Tartrate-resistant acid phosphatase (TRAP) staining was conducted to detect osteoclasts, and expression of osterix (OSX), type I collagen (Col I), type II collagen (Col II) and vascular endothelial growth factor (VEGF) were evaluated by immunochemistry. OVX affected the body's metabolism but INS did not, as the body weight increased and uterus weight decreased in OVX and COM mice compared to CON and INS mice. OVX, INS, and COM caused IVDD in various degrees at 12 weeks after surgery. However, the major pathogeneses of OVX- and INS-induced IVDD were different, which focused on endplate (EP) remodeling and annulus fibrosus (AF) collapse, respectively. OVX induced osteopenia of vertebra. In contrast, INS promoted the stress-adaptive increase of subchondral bone trabeculae. The COM produced a reproducible severe IVDD model with characteristics of sparse vertebral trabeculae, cartilaginous EP ossification, subchondral bone sclerosis, fibrous matrix disorder, angiogenesis, disc stiffness, as well as space fusion. Additionally, all groups had elevated bone and cartilage turnover compared with CON group, as the quantity of trap + osteoclasts and the osteogenic OSX expression increased in these groups. Likewise, the VEGF expression levels were similar, accompanied by the altered matrix expression of disc, including the changed distribution and contents of Col II and Col I. The findings suggested that the composite mouse model to some extent could effectively mimic the interactions of biology and mechanics engaged in the onset and natural course of IVDD, which would be more compatible with the IVDD of elderly with vertebral osteoporosis and spinal instability and benefit to further clarify the complicated mechanobiological environment of elderly IVDD progression.

Protective Effect of Cerebrospinal Fluid Containing Tongqiao Huoxuetang on Brain Microvascular Endothelial Cells from Rats with Oxygen Glucose Deprivation/Reoxygenation Injury / 中国实验方剂学杂志

Objective:To investigate the protective effect of cerebrospinal fluid containing Tongqiao Huoxuetang (TQHXT) on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (BMECs), in order to explore the underlying mechanisms. Method:Primary BMECs were extracted by enzymatic digestion, and the cells were randomly divided into six groups: the normal control group, the OGD/R group, the TQHXT group（20%）, the nimodipine（NMDP） group (10 μmol·L-1), the cabozanix group (1 μmol·L-1) and the combination group. Except for the normal control group, the cells in the other groups were rapidly reoxygenated for 24 h after 2 h of oxygen-glucose deprivation, the OGD/R modeling was performed, and the rats were administered with drugs by groups. BMECs were identified by cell immunofluorescence staining, morphological and ultrastructural changes of OGD/R-induced BMECs were observed, and changes in cell transmembrane resistance (TEER) were detected. The levels of nitric oxide (NO), the activity of lactate dehydrogenase (LDH), the fluorescence intensity of reactive oxygen species (ROS) and the content of tissue-type plasminogen activator (tPA) were measured with kits. Intracellular Ca2+ concentration and cell apoptosis were detected by flow cytometry, and the expression of CD34 was observed. The protein expressions of zonula occluden-1 (ZO-1), vascular endothelial growth factor (VEGF), adhesion kinase (FAK), and Paxillin were detected by Western blot. Result:Compared with the normal control group, the cells in the OGD/R group were shrinking and rounded, TEER value and ZO-1 protein expression in cells were significantly decreased, the contents of NO, LDH and ROS in cells were significantly increased, the content of tPA was significantly decreased, the concentration of Ca2+ and the apoptosis in the cells were significantly increased, CD34 was expressed in cells, and the protein expressions of VEGF, FAK and Paxillin were significantly increased (P<0.01). Compared with the OGD/R group, cell damage in the TQHXT group was significantly improved, the TEER value and ZO-1 protein expression in cells were significantly increased, the contents of NO, LDH and ROS in cells were significantly reduced, the content of tPA was significantly increased, the concentration of Ca2+ and the apoptosis in the cells were significantly reduced, CD34 expression increased in cells, and the protein expressions of VEGF, FAK and Paxillin were significantly increased (P<0.05，P<0.01). Conclusion:CSF containing TQHXT protects BMECs from OGD/R injury possibly by promoting angiogenesis through the VEGF-VEGFR2/FAK/Paxillin signaling pathway.

High-Quality Boron Nitride Nanosheets and Their Bioinspired Thermally Conductive Papers.

Hexagonal boron nitride has displayed increased potential in heat dissipation applications due to its desirable high thermal conductivity and remarkable thermal stability. However, the large-yield and high-quality preparation of boron nitride nanosheets (BNNSs) has been still an enormous challenge. In present work, we developed a universal exfoliation strategy to synthesize few-layer and defect-free BNNSs, which involved the intercalation of hexafluorosilicates/sodium hydroxide into BN crystals followed by exfoliation through a mild stirring process. The yield and concentration of as-obtained BNNS reached up to 78.5% and 12.78 mg/mL, respectively. More importantly, this method has been proven to exfoliate other layered materials like graphene (G), MoS2, and WS2. These as-obtained BNNSs can be directly used for constructing freestanding papers with high thermal conductivities. Typically, the thermal conductivities of the BNNS-G hybrid paper were up to 63.5 W/mK along the in-plane direction and 7.4 W/mK along the through-plane direction. According to the thermal interface materials performance measures, BNNS-G hybrid paper shows great promising applications for heat transfer in integrated circuit packaging.